# Driver Genes for Engineered Rotator Cuff Development

> **NIH NIH R01** · PURDUE UNIVERSITY · 2021 · $479,770

## Abstract

Rotator cuff tears affect over 15% of Americans and impair shoulder joint biomechanics and function. Following
repair of symptomatic tears, functional deficits frequently persist and re-tears are common, due to the complex
anatomy and high functional demands on the rotator cuff tendons. Rotator cuff tendon tissue engineering
research is focused on devices to improve immediate mechanical support to the repair and to stimulate early
and rapid tendon regeneration rather than scarring and fibrosis, particularly for the supraspinatus tendon (SST),
the most commonly torn tendon in the rotator cuff. Aligned electrospun scaffolds that mimic both the highly
aligned medial region of the SST, and bi-axially aligned electrospun scaffolds that mimic the multi-axially aligned
isotropic anterior region of the SST have been evaluated with promising results when seeded with adipose-
derived stem cells (ASCs). However, progress in this area of rotator cuff tendon engineering and in other areas
of tendon research is hindered by the lack of definitive markers for SST or for its regional heterogeneity, the lack
of understanding to what extent ASCs are tenogenic and can assume the identity of tendon fibroblasts, the lack
of specific markers for tendon fibroblast identity and tenogenic differentiation, and by a lack of markers for tendon
maturation and response to mechanical loading in engineered tendon. Therefore, is it difficult to assess how
successful current tendon tissue engineering approaches really are, or to predict how well tendon tissue
engineered approaches will function in translation when autologous or allogeneic ASCs from diverse human
populations are used to enhance rotator cuff repair via augmentation or interposition with engineered tendon
devices. These studies will evaluate the epigenome (methylome), transcriptome, proteome, lipidome,
metabolome and phenome (phenotype) of native human SST and donor-matched tissue engineered tendon
produced from SST fibroblasts and ASCs. Bioinformatics approaches will be used to integrate the data to an
integrated multiome, which will then be used with machine learning approaches to extract key causal ‘driver’
genes, or tendon specific genes or molecules responsible for: 1) SST heterogeneity between medial and anterior
regions. 2) Tendon cell identity and the extent of tenogenesis by ASCs on electrospun scaffolds. 3) The
heterogenetic response by ASCs on uni- vs. bi-axially aligned electrospun scaffolds that mimic the native
heterogeneity of the SST. 4) The response of engineered tendon to dynamic loading. Identified driver genes or
molecules will be validated though over-expression or silencing approaches, thus providing therapeutic targets
for manipulation to enhance tenogenesis, and engineered tendon development and maturation. Together these
innovative studies will provide a template for improved external validity of benchtop tendon tissue engineering
and pre-clinical studies towards successful translation in div...

## Key facts

- **NIH application ID:** 10098302
- **Project number:** 5R01AR073882-03
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Dianne Little
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $479,770
- **Award type:** 5
- **Project period:** 2019-03-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10098302

## Citation

> US National Institutes of Health, RePORTER application 10098302, Driver Genes for Engineered Rotator Cuff Development (5R01AR073882-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10098302. Licensed CC0.

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